This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a Phase 1, open-label, single-dose study in approximately 35 subjects with PKU who are 16-50 years old. Seven cohorts are planned, each consisting of five subjects;the cohorts as planned will receive one of the following doses of rAvPAL-PEG administered subcutaneously: 0.001, 0.003, 0.01, 0.03, 0.1, 0.3, and 1.0 mg/kg. Each dosing cohort will be assessed sequentially until the final does is evaluated or any of the stopping criteria are reached. Stopping criteria are as follows: for subject one in cohort one, drug related adverse events with CTCAE grad 4 toxicity. For subject 1 in cohort 1, reduction of blood phenylalanine to, 120 micromoles/L while subject is maintaining consistent dietary Phe intake. For cohorts 1 through 7 adverse events with CTCAE grade 3 or greater toxicity in 2 or more subjects within a cohort. After sutyd drug administration, the subject will e followed for a total of 42 days with visits to the GGCRC or Metabolic Outpatient Clinic depending on the day of the week the study visit falls on. Diet will not be modified while the subject is in the study. HYPOTHESIS: To assess the safety and tolerability fo single, subjcutaneous injections of rAVPAL-PEG in subjects with PKU.